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A. Spanò, C. Nucci, A. Cerulli, R. Tartaglione, L. Morrone, G. Bagetta; Evidence that Matrix Metalloproteinases are Involved in High Intraocular Pressure-Induced Retinal Ganglion Cell Death. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4206.
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to investigate the mechanisms of retinal ganglion cell (RGC) death and its relation to matrix metalloproteinases (MMP) activation in a model of high intraocular pressure (IOP)-induced ischemia.
In Sprague-Dawley rats, IOP was increased unilaterally to 120 mmHg for 45 minutes by elevating a saline reservoir connected to the eye. Test animals (n=3 per group) received injections (i.p. twice daily) of MK801, a NMDA receptor antagonist, GYKI52466, a non-NMDA receptor antagonist, or L-NAME, an inhibitor of nitric oxide (NO) synthase. A fourth group (n=3) received an intravitreal injection of GM6001, a MPP inhibitor. Control animals (n=3 per group) received injections of saline (i.p. or in the vitreous). After 24 hours of reperfusion, animals were sacrificed and retinal sections were processed for RGC counting as previously described (Nucci et al Neurotoxicology 2005). In a second set of experiments, extracellular glutamate was monitored during and after high-IOP induced ischemia using a microdialysis probe placed into the retina by means of high-performance liquid chromatography (Nucci et al Neurotoxicology 2005).
High IOP-induced ischemia increases intraretinal glutamate that peaks by approximately 90% at 130 min after reperfusion and reduces RGC by 28% compared to sham-operated eye. Injections of MK801, GYKI and L-NAME reduced the percentage of RGC loss to 2.6, 14.6 and 11.5% respectively. Similarly, intravitreal injection of GM6001 reduced RGC loss to 8.7%.
Our data indicate that during high IOP-induced ischemia excessive release of glutamate may induce RCG death by abnormally stimulating NMDA and non-NMDA receptors with consequent release of NO and activation of MMP.Table of ContentsSECTION. PHARMACOLOGY
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